A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial.
Authors: Kevin Kalinsky, Melissa Kate Accordino, Codruta Chiuzan, Prabhjot Singh Mundi, Meghna S. Trivedi, Yelena Novik, Amy Tiersten, George Raptis, Lea N. Baer, Sun Young Oh, Amelia Bruce Zelnak, Kari Braun Wisinski, Eleni Andreopoulou, William John Gradishar, Erica Stringer-Reasor, Sonya A. Reid, Anne O'Dea, Ruth O'Regan, Katherine D. Crew, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2022)

LBA1004 Background: CDK 4/6i has demonstrated benefit in progression free survival (PFS) and overall survival (OS) in pts with HR+, HER2- MBC when combined with endocrine therapy (ET). While observational data demonstrate a potential benefit of continuing CDK 4/6i and switching ET at progression, no prospective trials have evaluated this approach. We conducted a phase II, multi-center, randomized, trial to evaluate the efficacy of fulvestrant or exemestane +/- ribociclib in pts with HR+HER2- MBC whose cancer previously progressed on any CDK 4/6i + any ET. Methods: In this investigator-initiated, phase II, double-blind, placebo-controlled trial, men or women with measurable or non-measurable HR+/HER2- MBC whose cancer progressed during CDK 4/6i and ET were randomized 1:1 to fulvestrant or exemestane +/- ribociclib. Pts treated with prior fulvestrant received exemestane as ET in the randomization; if prior exemestane fulvestrant was the ET; if neither, fulvestrant or exemestane was per investigator discretion, though fulvestrant was encouraged. PFS was the primary endpoint, defined as time from randomization to progression of disease or death. A one-sided log-rank test with a sample size of 120 randomized and evaluable pts with a significance level alpha of 2.5%, achieves 80% power to detect an effect size (difference in PFS) of 3 months. Results: Of the 120 randomized evaluable pts, 1 pt was removed due to not taking ET along with ribociclib/placebo. All but 1 pt was female, the median age was 57.0 years, 88 pts (74%) were white, and 21 (17.6%) were Hispanic. For ET, 99 pts received fulvestrant (83%) and 20 pts exemestane (17%). In terms of prior CDK 4/6i, 100 pts previously received palbociclib (84%), 13 pribociclib (11%), 2 abemaciclib (2%), and 4 palbociclib and another CDK 4/6i (3%). There was a statistically significant PFS improvement for pts randomized to fulvestrant or exemestane + ribociclib [median: 5.33 months, 95% CI (Confidence Interval): 3.25–8.12 months] vs. placebo (median: 2.76 months, 95% CI: 2.66–3.25 months): Hazard Ratio (HR) = 0.56 (95% CI: 0.37-0.83), p = 0.004. Similar results were seen in the subset of pts treated with fulvestrant, with a median PFS for those randomized to ribociclib (5.29 months) vs. placebo (2.76 months), HR = 0.59 (95% CI: 0.38-0.91), p = 0.02. At 6 months, 42% were progression-free on the ribociclib arm vs. 24% on placebo. At 12 months, 25% were progression-free on the ribociclib arm vs. 7% on placebo. Additional endpoints will be reported, including overall response rate and safety. Conclusions: In this randomized, placebo-controlled trial, there was a significant PFS benefit for pts with HR+/HER2- MBC to switch ET and receive ribociclib after progression on CDK 4/6i. Clinical trial information: NCT02632045.